Murine dendritic epidermal T cells (DETC) were recently reported to express T-cell receptor (TCR)-γ/δ chains. In a search for the human equivalent of these cells, we tested normal and lesional skin ...with MoAb which react with the TCR-γ/δ heterodimer. We performed indirect immunofluorescence (IF) on epidermal sheets, and alkaline- phosphatase-anti-alkaline-phosphatase complex (APAAP) on epidermal cell smears. Frozen skin sections from normal skin and various cutaneous lymphocyte infiltrates were also studied. A few CD3+ T lymphocytes were consistently found in normal epidermis. Most of these cells appeared to be TCR-α/β+, and some CD4+ or CD8+. On epidermal sheets and cell smears, only a very small TCR-γ/δ+ cell population was visualized (less than 0.1% of the total). On normal skin sections, we observed 0 to 3 γ/δ+ cells per section. When present, they were often located in the epidermal basal layer, and were round or dendritic. Double immunolabeling revealed that γ/δ+ cells differed from CD1+ Langerhans cells, and that they had a similar phenotypic pattern as γ/δ+ peripheral lymphocytes (PBL): CD2+, CD3+, CD4-, and CD8-. Immunostaining from various inflammatory skin lesions showed that the dermal infiltrates included CD3+ T lymphocytes but virtually no γ/δ+ cells. Only a few γ/δ+ cells were found in some end-evolutive infiltrates. Taken together, these results strongly suggest that normal human epidermis occasionally harbors TCR-γ/δ complex bearing lymphocytes, which constitute a small fraction of the CD3+ cutaneous T lymphocytes. Despite their common location and TCR expression, there is presently no evidence that these human cutaneous TCR-γ/δ bearing T cells are the equivalent of murine DETC.
We describe a unique case of human T-lymphotropic virus 1 (HTLV-1)-associated infective dermatitis-like lesions in systemic lupus erythematosus. This suggests that some lupus patients may have ...immunological abnormalities resembling to those described in chronic HTLV-1 infection.
A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous ...lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur.
We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell‐lymphomas diagnosed during a 5‐year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease‐free with an overall median follow‐up of 30 months. Histologically, some distinctive signs such as epidermal pseudoepitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.
Acute graft-versus-host reaction after allogeneic bone marrow transplantation has been reported to induce toxic epidermal necrolysis. To assess the respective role of acute graft-versus-host disease ...and of drug reaction in this setting, we retrospectively reviewed nine cases of toxic epidermal necrolysis that occurred in a series of 152 allogenic bone marrow recipients. In five cases visceral involvement was suggestive of acute graft-versus-host disease without any drug more than "doubtfully" suspected. In four cases extracutaneous symptoms were absent or mild and suspect drugs (mainly sulfonamides) had been administered with a timing suggestive of "possible" causality. All nine patients died, mainly from infection possibly aggravated by high doses of corticosteroids. We conclude that toxic epidermal necrolysis may be more frequent than generally thought after bone marrow transplantation and has a poor prognosis. It seems to be related to a drug reaction to sulfonamides as often as to acute graft-versus-host disease.
Syndrome de sézary Bagot, Martine; Imbert, Michèle
Revue française des laboratoires,
2/2004, Letnik:
2004, Številka:
360
Journal Article
La cellule de Sézary est un lymphocyte mature à noyau convoluté, cérébriforme, en cytologie et en microscopie électronique. Elle constitue l'un des éléments du diagnostic de syndrome de Sézary, ...défini cliniquement par la survenue rapide d'une érythrodermie très prurigineuse et d'adénopathies disséminées. Les cellules de Sézary peuvent également traduire l'envahissement du sang par un lymphome cutané de type mycosis fongoïde. Dans un contexte clinique évocateur, l'examen du frottis de sang, quel que soit le résultat de l'hémogramme, est essentiel pour identifier un pourcentage significatif de cellules caractéristiques. Les cellules de Sézary ont dans la majorité des cas un phénotype de lymphocytes T mémories CD2
+, CD3
+, CD4
+, CD5
+, CD8
−, CD45RO
+, CD45RA
−, TCR α/β
+, mais elles peuvent également avoir un phénotype CD8
+CD4
− ou CD4
+CD8
+ et/ou présenter une perte d'expression des antigènes CD2, CD3, CD4, ou CD5. Chez les patients ayant un syndrome de Sézary, on observe souvent une augmentation de la population lymphocytaire CD4
+. Il existe une augmentation de la population CD4
+CD7
−, mais les cellules tumorales ont été identifiées aussi bien dans la population CD4
+CD7
+ que dans la population CD4
+CD7
−. Les cellules de Sézary appartiennent à la sous-population lymphocytaire CD4
+CD26
−, mais il n'existe pas de marqueur phénotypique spécifique des cellules de Sézary. L'IL-7 est un facteur de croissance des cellules de Sézary, qui peut permettre d'établir des lignées de lymphocytes T tumoraux. Nous avons récemment identifié trois nouveaux antigénes de surface coexprimés par les cellules de Sézary. Le récepteur NK CD158k/KIR3DL2/p140, présent sur une sous-population de lymphocytes NK et CD8, est exprimé par les lignées tumorales T et par des lymphocytes CD4 de malades ayant un syndrome de Sézary. SC5 est un nouveau marqueur d'activation normalement expriméà la surface d'une sous-population minoritaire de lymphocytes circulants. L'expression de SC5 est augmentée chez les patients ayant un syndrome de Sézary, et corrélée à l'expression de p140. ILT-2/CD85j est un autre récepteur inhibiteur exprimé par les lymphocytes T tumoraux. L'engagement des molécules SC5 ou ILT-2 entraîne le recrutement de la molécule SHP-1 et l'inhibition de la prolifération cellulaire induite via le complexe CD3/TCR. L'expression de ces récepteurs inhibiteurs de l'activation ne veut pas dire qu'ils exercent leur effet inhibiteur de la prolifération in vivo, mais qu'ils sont peut-être le témoin de l'absence d'inhibition. D'autre part, l'augmentation de l'expression de bcl-2 induite par les cytokines pourrait jouer un rôle important pour maintenir la survie des cellules de Sézary. Ainsi, l'identification de ces nouveaux antigènes sur les cellules tumorales ouvre de nouvelles perspectives pour la physiopathologie et le traitement des malades ayant un syndrome de Sézary.
The Sezary cell is a mature lymphocyte with a convoluted, cerebriform nucleus on cytomorphologic and ultrastructural samples. It is a major diagnostic feature of Sezary syndrome, clinically defined by the rapid onset of a pruriginous erythroderma with diffused adenopathies. Sezary cells can also reveal blood involvement by tumor cells in patients with mycosis fungoides. In a suggestive clinical context, peripheral blood smear examination is essential, whatever the results of the total blood count, to identify a significant percentage of characteristic cells. Most Sezary cells have a phenotype of mature memory T-lymphocytes, CD2
+, CD3
+, CD4
+, CD5
+, CD8
−, CD45RO
+, CD45RA
−, TCR α/β
+, but rarely they can also exhibit a CD8
+CD4
− or CD4
+CD8
+ phenotype, and/or a lack of expression of CD2, CD3, CD4, or CD5 antigens. Patients with a Sezary syndrome often have an increase in CD4
+ lymphocytes. The CD4
+CD7
− population is also increased, but tumor cells have been identified both in the CD4
+CD7
+ and in the CD4
+CD7
− populations. Sezary cells are found in the CD4
+CD26
− population, but there are yet no specific phenotypic markers of Sezary cells. IL-7 is a growth factor for Sezary cells, and can induce the establishment of long-term tumor T-cell lines. We recently identified three other surface antigens on Sezary cells. The Natural Killer (NK) receptor CD158k/KIR3DL2/p140, normally expressed by NK and CD8
+ T-cells was detected on the surface of CTCL cell lines as well as on freshly isolated CD4
+ peripheral blood lymphocytes from SS patients. SC5 is a newly described activation-related intracellular inhibitory receptor expressed on the surface of a minor PBL subset. We found that SC5 expression was significantly increased in SS cells and correlated to p140 expression, ILT-2/CD85j is another inhibitory receptor expressed by tumor T-lymphocytes. Both SC5 and ILT-2 molecules are functional on CTCL cells, as their triggering in vitro leads to the recruitement of SHP-1 and to the specific inhibition of CTCL malignant cell proliferation induced by CD3/TCR stimulation. The expression of these antigens and the cytokine-induced upregulation of bcl-2 could partly explain the survival and the inhibition of the apoptosis of Sezary cells. Their identification on circulating SS tumor cells might be of importance both for the understanding of CTCL pathophysiology and for the treatment of SS patients.
To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides ...while increasing cutaneous tolerance.
Prospective nonrandomized study conducted from November 1999 to November 2002.
Eleven university or hospital dermatology departments in France.
Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5).
Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period.
The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response.
Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months.
A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.
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